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71.
c-Jun expression after axotomy of corneal trigeminal ganglion neurons is dependent on the site of injury 总被引:1,自引:0,他引:1
The proto-oncogene c-Jun has been implicated in the control of neuronal responses to injury and in axonal growth during regenerative processes. We have investigated the expression of c-Jun during normal terminal remodelling in trigeminal ganglion neurons innervating the cornea and after acute injury of epithelial nerve terminals or parent axons. Remodelling and rearrangement, or damage limited to corneal epithelium endings, was not a trigger for activation of c-Jun expression. However, injury of parent axons in the stroma or in the orbital ciliary nerves induced c-Jun expression in 50% of the population of corneal neurons, which included all of the large myelinated and 20% of the small neuropeptide-containing corneal neurons. This suggests that c-Jun expression in trigeminal ganglion neurons is not associated with normal remodelling or regeneration of peripheral nerve terminals, and that it takes place only when parent axons are injured. A substantial number of damaged neurons do not express c-Jun, indicating that in primary sensory neurons, injury and regeneration may not always be coupled to the expression of this proto-oncogene. 相似文献
72.
Lateral transperitoneal laparoscopic adrenalectomy 总被引:7,自引:0,他引:7
Shichman SJ Herndon CD Sosa RE Whalen GF MacGillivray DC Malchoff CD Vaughan ED 《World journal of urology》1999,17(1):48-53
Several laparoscopic approaches to the adrenal gland have been described. The lateral transperitoneal approach has several
distinct advantages when contrasted with other techniques for laparoscopic adrenalectomy (LA). We present our technique and
results obtained in 50 consecutive transperitoneal LAs. We review 50 consecutive laparoscopic adrenalectomies (28 female,
19 male) performed from 1993 to 1998. S.J. Shichman or R.E. Sosa was either the primary surgeon or the first assistant for
all cases. The lateral transperitoneal approach described below was used in all cases. Indications for adrenalectomy included
Cushing's syndrome (13), aldosteronoma (15), pheochromocytoma (7), nonfunctioning adenoma (11), hyperplasia (2), and 1 case
each of Carney's syndrome and metastasis to the adrenal gland. We performed 5 bilateral, 22 left, and 18 right laparoscopic
adrenalectomies. The average time needed for bilateral adrenalectomy was 503 min (range 298–690 min); for left adrenalectomy,
227 min (range 121–337 min); and for right LA, 210 min (range 135–355 min). We demonstrated a yearly trend in lower operative
times. The largest adrenal gland removed measured 13.8 × 6.7 × 3.5 cm. Intraoperative blood loss was low. Only one patient
received a blood transfusion. Conversion to open adrenalectomy was not required. Postoperative analgesic requirements were
low. The average length of stay was 3.8 days for bilateral LA and 3 days for unilateral LA. Complications occurred in 5 patients
(2 wound infections, 2 hematomas, and 1 pleural effusion). There was no mortality. Lateral transperitoneal adrenalectomy is
a safe and efficient technique for the removal of functional and nonfunctional adrenal masses. This technique is associated
with low morbidity, a minimal postoperative analgesic requirement, and a short hospital stay and, in our opinion, is more
versatile than the retroperitoneal approach. 相似文献
73.
Howard Hochster Ruth Oratz David S. Ettinger Ernest Borden 《Investigational new drugs》1999,16(3):259-263
Purpose: Didemnin B is a novel marine natural product cyclic depsipeptide containing unusual amino acid moieties. This agent demonstrates promising preclinical antitumor activity, including activity against B16 melanoma and against melanoma isolates in the human tumor stem cell assay.Methods: We conducted a phase II study of Didemnin B, given in Cremophor, at a starting dose of 4.2 mg/m2/IV q 28 days. Patients with measurable metastatic or advanced malignant melanoma were eligible. All patients were previously untreated with chemotherapy and had performance status 0 or 1. Doses were escalated to 4.9 and 5.6 mg/m2 in cycles 2 and 3, respectively.Results: Nineteen patients were entered and treated with a median of one cycle per patient. Eight of these patients went off study for toxicity including 7 with anaphylactoid reactions in the first or second cycle. One patient went off study after 3 cycles with severe myopathy, a newly described toxicity. Two were not evaluable for response and five were considered stable, including one patient with a transient PR of soft tissue disease in the first cycle. Another patient had stable disease for twelve cycles before progressing and one went off study electively after 3 cycles, for a total of 7 patients with stable disease. One patient with a measurable partial remission (PR) and went off study after three cycles due to severe myopathy, a then newly-described toxicity. No hematologic toxicity was seen. Nausea and vomiting were controlled with anti-emetics.Conclusions: This study was indeterminate with respect to the activity of Didemnin B in melanoma. Signs of activity were seen, particularly in soft tissue masses, though a large number of patients could not be evaluated fully for activity due to the occurrence of anaphylactoid reactions. This study does not preclude a clinically important level of activity for Didemnin B. 相似文献
74.
Berthe L. F. van Eck-Smit Ernst E. van der Wall Patrick P. A. M. Verhoeven Suzanne Poots Aeilko H. Zwinderman Ernest K. J. Pauwels 《European journal of nuclear medicine and molecular imaging》1996,23(2):188-194
As several reinjection procedures have shown encouraging results in terms of imaging, we investigated whether the kinetics of thallium-201 would differ between the standard stress-redistribution-reinjection approach and the stress-immediate reinjection approach. In 53 consecutive patients with undiagnosed chest pain, 75 MBq (2 mCi)201Tl was injected at maximal exercise. In 26 of these patients (group I), 37 MBq (1 mCi)201Tl was reinjected immediately after completing the exercise images (the immediate reinjection procedure) and in 27 patients (group II), 37 MBq (1 mCi)201Tl was reinjected after completing 3-h redistribution images (the standard reinjection procedure). Mean peak201Tl blood activity after exercise was 17.7±12.5 kBq/ml (4.8±3.4 mCi/ml) for group I versus 16.4±9.2 kBq/ml (4.4±2.5 mCi/ml) for group II (NS). The relative increase in201Tl blood activity after reinjection of half the initial dose [37 MBq (1 mCi)] exceeded 50% of the initial peak in both groups. The relative amount of201Tl delivered to the myocardium was assessed by the area under the curve after both exercise and reinjection, and was 117%±72% for group I and 112%±73% for group II (NS). Blood clearance of201Tl was at least biexponential. Mean early decay constants (1) after exercise and reinjection were 0.30±0.18 min–1 and 0.22±0.046 min–1 respectively for group I (T
1/2 2.3 min and 3.2 min respectively, NS), and 0.30±0.12 min–1 and 0.24±0.07 min–1 respectively for group II (T
1/2 2.3 min and 2.9 min respectively, NS). For both procedures no significant differences were found between 1 after exercise and 1 after injection. The mean late clearance (2) from the blood was 0.032±0.056 min–1 and 0.012±0.012 min–1 respectively for group I (T
1/2 21.6 min and 57.7 min respectively, NS), and 0.036±0.030 min–1 and 0.014±0.014 min–1 respectively for group II (T
1/2 19.3 min and 49.5 min respectively, NS). Also, no significant differences were found between 2 after exercise for both groups and between 2 after reinjection for both groups. We conclude that reinjection of 37 MBq (1 mCi)201Tl (half the initial dose) results in a relative increase in the initial peak and a relative increase in the amount of201Tl delivered to the myocardium of more than 50% for both the standard and the immediate reinjection procedure. The clearance of201Tl from the blood was not influenced by exercise or by the time of reinjection. Based on201Tl kinetics as measured in the peripheral blood, there is no reason to postpone reinjection until 3–4 h following exercise. 相似文献
75.
Tom Bougsty Prudy Marshall Ernest Chavez 《Administration and policy in mental health》1983,10(4):272-287
Energy-impacted communities experience rapid population growth due to energy resource production. A high prevalence of psychological and social problems are frequently reported in such communities. The present research employed a standardized instrument and random sampling in a community needs assessment to document high prevalence of problems in an energy-impacted town that has attempted to plan for rapid growth. At least 35 percent of the men and 25 percent of the women randomly sampled in the community reported elevated levels of psychological distress; 48 percent of the men admitted to alcohol problems. How the local mental health center utilized the needs assessment results to improve services, obtain funding for needed programs, and generally promote the community's quality of life is described. Recommendations for social planning that go beyond the brick and mortar approach to community planning are provided; prevention services are recommended above traditional remedial mental health services for such circumstances.Tom Bougsty, Ph.D., and Prudy Marshall, Ph.D., are both at the SEW Mental Health Center in Cheyenne WY. Ernest Chavez, Ph.D., is at the Colorado State University at Fort Collins, CO. Requests for reprints should be directed to the first author at 118 W. 4th Ave., Cheyenne, WY 82001. 相似文献
76.
Changes in the endogenous synthesis of inositol 1,4,5-trisphosphate (IP3) mass have been quantitated in human peripheral neutrophils stimulated with FMLP, LTB4 and PAF using a recently described, highly specific radioreceptor assay. Each agonist induced a concentration-dependent synthesis of IP3 which was detectable within 10 seconds after stimulation. IP3 production was short-lived, returning to basal levels within 90 seconds. The maximal stimulated level of IP3 in response to FMLP and LTB4 was 30–50 pmoles/107 neutrophils. PAF was more effective (100 pmoles IP3/107 neutrophils). The response to FMLP was inhibited by pertussis toxin, but was unaffected by cholera toxin. Pretreatment with cytochalasin B did not enhance IP3 synthesis. These findings are generally consistent with previous studies employing [3H]myo-inositol-prelabeled cells, and provide one of the first measurements of IP3 synthesis by mass in agonist-stimulated human neutrophils. 相似文献
77.
The termwell-baby clinic (literally, a clinic that concerns itself with healthy infants) is probably better known in the United States, where such clinics exist, than in central Europe, where, on the whole, they do not. For the convenience of readers accustomed to it a formal definition is proffered: A well-baby clinic is a service center, with emphasis on physical and mental hygiene and prophylaxis, where mothers are seen with their young, healthy infants and helped to understand and manage the infant's unfolding maturation [1: p. 5] and development [1: p. 5]. This may serve to differentiate well-baby clinics, on the one hand, from clinics for sick children and child guidance clinics (usually resorted to after disturbances have emerged) and, on the other hand, from maternity and child welfare clinics, whose primary object is to safeguard physical health. (Maternity and child welfare clinics are also known as family health clinics, child health clinics, and infant welfare clinics. The extent to which they can cater to the psychological needs of mother and infant depends on their staff's training.)This paper forms part of a research project entitled Childhood Pathology: Impact on Later Mental Health, which is being conducted at the Hampstead Child-Therapy Course and Clinic, London. The project is financed by National Institute of Mental Health Grant MH-05683-11. Appreciation is expressed to Anna Freud, Elizabeth Model, Professor A. J. Solnit, and Dr. Josefine Stross for their valuable suggestions. The authors acknowledge with gratitude the freedom to quote from the Well-Baby Clinic's annual reports, compiled by the clinic's pediatrician, Dr. Josefine Stross, with the active help of her past assistants, Annemarie Curson, Manna Friedmann, and Joyce Robertson, and her present assistants, Irene Freud and E. Model.This paper was originally published in German, in volume 2 of theJahrbuch der Psychohygiene, Ed. Gerd Biermann, Ernst Reinhardt Verlag, München/Basel, 1974. 相似文献
78.
Joseph G Rajendran David A Mankoff Finbarr O'Sullivan Lanell M Peterson David L Schwartz Ernest U Conrad Alexander M Spence Mark Muzi D Greg Farwell Kenneth A Krohn 《Clinical cancer research》2004,10(7):2245-2252
PURPOSE: The aim of this study is to compare glucose metabolism and hypoxia in four different tumor types using positron emission tomography (PET). (18)F-labeled fluorodeoxyglucose (FDG) evaluates energy metabolism, whereas the uptake of (18)F-labeled fluoromisonidazole (FMISO) is proportional to tissue hypoxia. Although acute hypoxia results in accelerated glycolysis, cellular metabolism is slowed in chronic hypoxia, prompting us to look for discordance between FMISO and FDG uptake. EXPERIMENTAL DESIGN: Forty-nine patients (26 with head and neck cancer, 11 with soft tissue sarcoma, 7 with breast cancer, and 5 with glioblastoma multiforme) who had both FMISO and FDG PET scans as part of research protocols through February 2003 were included in this study. The maximum standardized uptake value was used to depict FDG uptake, and hypoxic volume and maximum tissue:blood ratio were used to quantify hypoxia. Pixel-by-pixel correlation of radiotracer uptake was performed on coregistered images for each corresponding tumor plane. RESULTS: Hypoxia was detected in all four patient groups. The mean correlation coefficients between FMISO and FDG uptake were 0.62 for head and neck cancer, 0.47 for breast cancer, 0.38 for glioblastoma multiforme, and 0.32 for soft tissue sarcoma. The correlation between the overall tumor maximum standardized uptake value for FDG and hypoxic volume was small (Spearman r = 0.24), with highly significant differences among the different tumor types (P < 0.005). CONCLUSIONS: Hypoxia is a general factor affecting glucose metabolism; however, some hypoxic tumors can have modest glucose metabolism, whereas some highly metabolic tumors are not hypoxic, showing discordance in tracer uptake that can be tumor type specific. 相似文献
79.
Neil E Martin Thomas B Brunner Krystina D Kiel Thomas F DeLaney William F Regine Mohammed Mohiuddin Ernest F Rosato Daniel G Haller James P Stevenson Debbie Smith Barnali Pramanik Joel Tepper Wesley K Tanaka Briggs Morrison Paul Deutsch Anjali K Gupta Ruth J Muschel W Gillies McKenna Eric J Bernhard Stephen M Hahn 《Clinical cancer research》2004,10(16):5447-5454
PURPOSE: Preclinical and clinical studies have demonstrated that inhibition of prenylation can radiosensitize cell lines with activation of Ras and produce clinical response in patients with cancer. The aim of this study was to determine the maximally tolerated dose of the dual farnesyltransferase and geranylgeranyltransferase I inhibitor L-778,123 in combination with radiotherapy for patients with locally advanced pancreatic cancer. EXPERIMENTAL DESIGN: L-778,123 was given by continuous intravenous infusion with concomitant radiotherapy to 59.4 Gy in standard fractions. Two L-778,123 dose levels were tested: 280 mg/m2/day over weeks 1, 2, 4, and 5 for dose level 1; and 560 mg/m2/day over weeks 1, 2, 4, 5, and 7 for dose level 2. RESULTS: There were no dose-limiting toxicities observed in the eight patients treated on dose level 1. Two of the four patients on dose level 2 experienced dose-limiting toxicities consisting of grade 3 diarrhea in one case and grade 3 gastrointestinal hemorrhage associated with grade 3 thrombocytopenia and neutropenia in the other case. Other common toxicities were mild neutropenia, dehydration, hyperglycemia, and nausea/vomiting. One patient on dose level 1 showed a partial response of 6 months in duration. Both reversible inhibition of HDJ2 farnesylation and radiosensitization of a study patient-derived cell line were demonstrated in the presence of L-778,123. K-RAS mutations were found in three of the four patients evaluated. CONCLUSIONS: The combination of L-778,123 and radiotherapy at dose level 1 showed acceptable toxicity in patients with locally advanced pancreatic cancer. Radiosensitization of a patient-derived pancreatic cancer cell line was observed. 相似文献
80.
Ernest C Borden Laurence H Baker Robert S Bell Vivien Bramwell George D Demetri Burton L Eisenberg Christopher D M Fletcher Jonathan A Fletcher Marc Ladanyi Paul Meltzer Brian O'Sullivan David R Parkinson Peter W T Pisters Scott Saxman Samuel Singer Murali Sundaram Allan T van Oosterom Jaap Verweij Jill Waalen Sharon W Weiss Murray F Brennan 《Clinical cancer research》2003,9(6):1941-1956
Sarcomas--like leukemias, which are also mesodermal malignancies--carry biological significance disproportionate to their clinical frequency. Identification of mutations and translocations associated with these tumors has illuminated aberrant signaling pathways that cause these diseases, determine their behavior, and are therapeutic targets. Activated receptor-associated tyrosine kinase c-kit, mutated in most gastrointestinal stromal tumors, has proven a clinically effective target for enzyme inhibition. A translocation involving a single gene family, consisting of EWS and related genes, has been identified in five different sarcomas, and its chimeric protein products could prove similarly amenable to inhibitors. Resolution of the histopathological complexity is being aided by data from molecular and chromosomal characterization. Improvements in imaging, definition of prognostic factors, and surgical and radiotherapeutic treatment have resulted in improved local control. Continued progress will depend on further adapting the rapidly evolving technologies of genomics and proteomics. It will also depend upon accurate histopathological diagnosis based on validated reagents and consistent methodologies applied to adequate tissue samples derived from patients with complete clinical data. Finally, multicenter, coordinated trials, such as those that occurred with assessment of imatinib mesylate in metastatic gastrointestinal stromal tumors, will assure the most rapid reductions in morbidity and mortality. 相似文献